Clinical Trials Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jul 19, 2025; 15(7): 105249
Published online Jul 19, 2025. doi: 10.5498/wjp.v15.i7.105249
Efficacy of Pediococcus acidilactici CCFM6432 in alleviating anhedonia in major depressive disorder: A randomized controlled trial
Du-Xing Li, Qi-Ming Hu, Chen-Chen Xu, Hong-Yu Yang, Ji-Kang Liu, Yi-Fan Sun, Gang Wang, Jun Wang, Zhen-He Zhou
Du-Xing Li, Yi-Fan Sun, Jun Wang, Zhen-He Zhou, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
Qi-Ming Hu, Chen-Chen Xu, Ji-Kang Liu, Jun Wang, Zhen-He Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
Hong-Yu Yang, Gang Wang, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, China
Hong-Yu Yang, Gang Wang, School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu Province, China
Co-corresponding authors: Jun Wang and Zhen-He Zhou.
Author contributions: Wang J and Zhou ZH contributed equally to this study as co-corresponding authors; Li DX, Sun YF, Liu JK, and Yang HY were responsible for investigation; Zhou ZH, Wang G, and Wang J were responsible for resources; Zhou ZH, Wang G, and Wang J were responsible for the methodology; Sun YF, Hu QM, Xu CC, and Liu JK were responsible for the formal analysis; Li DX, Hu QM, Xu CC, and Yang HY were responsible for data curation; Li DX was responsible for writing - original draft preparation; Wang J and Zhou ZH were responsible for writing - review and editing; Hu QM, Wang G, Xu CC, and Liu JK were responsible for visualization; Zhou ZH, Sun YF, and Wang J were responsible for supervision; Wang J and Zhou ZH were responsible for project administration; Wang J was responsible for funding acquisition; All authors have read and agreed to the published version of the manuscript.
Supported by the Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee, No. BJ2023086; and Wuxi Taihu Talent Project, No. WXTTP 2021.
Institutional review board statement: This study received approval from the Ethics Committee of Wuxi Mental Health Center and adhered rigorously to the principles of the Declaration of Helsinki.
Clinical trial registration statement: This study was retrospectively registered at https://www.chictr.org.cn/ (Registration No. ChiCTR2400093687; date of registration: December 10, 2024).
Informed consent statement: Informed consent was obtained from all subjects involved in the study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Wang, MD, PhD, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, No. 156 Qianrong Road, Binhu District, Wuxi 214151, Jiangsu Province, China. woodfish2@126.com
Received: January 16, 2025
Revised: March 28, 2025
Accepted: May 20, 2025
Published online: July 19, 2025
Processing time: 175 Days and 14.1 Hours
Abstract
BACKGROUND

Anhedonia, a hallmark symptom of major depressive disorder (MDD), is often resistant to common antidepressants. Preliminary evidence indicates that Pediococcus acidilactici (P. acidilactici) CCFM6432 may offer potential benefits in ameliorating this symptomatology in patients with MDD.

AIM

To further assess the efficacy of P. acidilactici CCFM6432 in alleviating anhedonia in patients with MDD, using a combination of objective and subjective assessment tools.

METHODS

Adult patients with MDD exhibiting anhedonic symptoms were enrolled and randomly assigned to two treatment groups: One receiving standard antidepressant therapy plus P. acidilactici CCFM6432, and the other receiving standard antidepressant treatment along with a placebo, for 30 days. Assessments were conducted at baseline and post-intervention using the Hamilton Depression Rating Scale (HAMD), Temporal Experience of Pleasure Scale (TEPS), and synchronous electroencephalography (EEG) during a "Doors Guessing Task." Changes in both clinical outcomes and EEG biomarkers, specifically the stimulus-preceding negativity (SPN) and feedback-related negativity amplitudes, were analyzed.

RESULTS

Of the 92 screened participants, 71 were enrolled and 55 completed the study (CCFM6432 group: n = 27; Placebo group: n = 28). No baseline differences were noted between the groups in terms of demographics, clinical assessments, or EEG metrics. A mixed-design analysis of variance revealed that the CCFM6432 group showed significantly greater improvements in both HAMD and TEPS scores compared to the Placebo group. Moreover, the CCFM6432 group demonstrated a significant increase in SPN amplitudes, which were inversely correlated with the improvements observed in HAMD scores. No such changes were observed in the Placebo group.

CONCLUSION

Adjunctive administration of P. acidilactici CCFM6432 not only augments the therapeutic efficacy of antidepressants but also significantly ameliorates the symptoms of anhedonia in MDD.

Keywords: Anhedonia; Probiotics; Depression; Event-related potentials; Reward processing

Core Tip: Anhedonia, a core symptom of major depressive disorder (MDD), often exhibits poor responsiveness to conventional antidepressants, substantially impairing long-term prognosis. In our randomized controlled trial, adjunctive administration of Pediococcus acidilactici CCFM6432 alongside standard antidepressants demonstrated marked improvements in anhedonia, particularly anticipatory deficits, among patients with MDD. Efficacy was quantified through the Temporal Experience of Pleasure Scale and task-specific electroencephalography biomarkers during the Guessing-Door Task, revealing enhanced reward anticipation neural signatures. These findings highlight the clinical potential of CCFM6432 in addressing anhedonia, with mechanistic implications for gut microbiota-brain axis modulation.